Recent research on artificial pancreas (AP) systems produced various AP technologies with good performance in clinical studies and indicated the need for improving the reliability of daily use of AP by patients. Reliable and robust AP systems can be designed by integrating multivariable monitoring, fault detection and diagnosis, sensor redundancy, and fault-tolerant control techniques to provide self-recovery, safeguards against failures and warnings and messages to users and medical care providers. The proposed research focuses on the development of a fault-tolerant AP that integrates these technologies, mitigates the risks in AP systems and functions at an acceptable level for BGC regulation until the diagnosed fault can be repaired or can provide safe transfer to manual operation of insulin pumps by the user. Our research focus is on the development of multivariable algorithms and software tools for performance monitoring, fault detection and diagnosis, control system performance assessment, analytical redundancy in sensors, control algorithms with fault-tolerance and recovery, and warning systems to users and care providers to a create fault-tolerant AP system. The critical characteristics of our approach are the use of physiological variable information to complement continuous glucose measurements, multivariable modeling, monitoring, diagnosis and control techniques, and recursive models and adaptive model-based control systems. A multivariable simulator with multiple inputs (glucose concentration and physiological variables) will also be developed to test the performance monitoring, FDD, sensor redundancy, and fault- tolerant control modules and assess the performance of fault-tolerant AP system. Clinical studies will be conducted to test the performance of various modules and of fault-tolerant AP system. They will also be used to assess the potential of quality of life improvements and reduction of fear of hypoglycemia in AP use. The proposed research will be collaboration between Ali Cinar - Illinois Institute of Technology, Elizabeth Littlejohn - Universiy of Chicago, and Laurie Quinn - University of Illinois at Chicago, in partnership with Medtronic Corporation and Body-Media, inc.